Recent advance in neuroscience is making clear the natural shape of neurotransmitters, substances deeply related to memory in the brain. It is said that some of these substances are neuropeptides containing prolines.
Recovery of the memory was reported by the dose of neuropeptide containing proline to an experimental amnesia rat (See Science 211, 601 (1981)).
On the other hand, it is presumed that these neuropeptide-hormones shall be metabolized by cerebral endogenous peptidases. Especially, prolyl endopeptidase (EC, 3.4.21.26) might take part in this metabolism closely (See J. Biochem., 94, 1179 (1983)).
From these facts, the studies were in progress that it should be possible to prevent or treat amnesia by inhibiting prolyl endopeptidase and suppressing the metabolism of neutrotransmitters. (See Protein, Nucleic acid and Enzyme 25(6), 513(1980); Nippon Nougei Kagaku Kaishi 58(11), 1147(1984); J. Neurochem., 41, 69(1983); ibid 42, 237(1984).)
For the purpose described above, several compounds were synthesized. For example, it is clear that N-benzyloxycarbonyl-glycyl-L-prolyl-chloromethane, N-benzyloxycarbonyl-L-prolyl-prolinal strongly inhibit prolyl endopeptidase (See J. Neurochem., 41, 69 (1983)). More recently, it is disclosed that compounds shown below are effective for the above purpose.
See Japanese Patent Kokai No. 60-188317, i.e. European Patent Publication No. 154353.
See Japanese Patent Kokai No. 61-37764; a compound wherein n is 5 is also disclosed by correction, i.e. European Patent Publication No. 172458.
See Japanese Patent Kokai No. 61-183297.
Most recently, five applications related to anti-amnesia agents having prolinal skeltons were published.
See Japanese Patent Kokai No. 61-238776, i.e. European Patent Publication No. 201742.
See Japanese Patent Kokai No. 61-238799, i.e. European Patent Publication No. 201743.
See Japanese Patent Kokai No. 62-84058, i.e. European Patent Publication No. 201743.
see Japanese Patent Kokai No. 62-148467, i.e. European Patent Publication No. 201741.